5588568 ASSOCIATION OF MANNOSE-BINDING LECTIN SERUM LEVEL AND PROMOTER GENE VARIANTS RS7096206 AND RS10031251 WITH FREQUENCY OF VASO-OCCLUSIVE EVENTS IN SICKLE CELL DISEASE PATIENTS; AN EGYPTIAN CROSS-SECTIONAL STUDY
Authors: M. El-Ghamrawy, N. El-Gharbawi, A. Soliman, M. Edward, G.A. Abd-Elmaksoud, O.Y. Abd El Dayem
Journal: HemaSphere (2023)

Background: Sickle cell disease (SCD) is a genetic blood disorder involving hemoglobin alterations, in addition to endothelial adhesion, thrombosis and inflammation. Low serum Mannose-binding lectin (MBL) levels can enhance SCD-related blood vessel inflammation as well as reduction of phagocytic activity, leading to sickled erythrocyte accumulation on vessel walls and impaired ability to combat infections. This may contribute to the vaso-occlusive (VOC) episodes. Aim: This work aimed to investigate serum MBL level and MBL promoter gene variants distribution among a cohort of Egyptian SCD patients and to describe their association with VOC events frequencies in the studied patients. Methods: This cross-sectional study included 88 steady-state Egyptian SCD patients aged 6-18 years diagnosed and followed up at Pediatric Hematology Unit, Cairo University Children Hospital. Informed consent was obtained willingly from all subjects or their guardians before enrolment in the study. MBL promoter (-221) (rs7096206) X/Y and (-550) (rs10031251) H/L gene variants were studied by Polymerase Chain Reaction- Restriction Fragment Length Polymorphism (PCR-RFLP) technique. Serum MBL level was assayed by ELISA technique with values <500ng/ml considered deficient. Results: The median serum MBL level in SCD patients was 130.9 ng/ml (IQR 71.2-323.9 ng/ml). Patients with serum MBL levels <500ng/ml were significantly older, had longer disease duration and higher rate of VOCs per year, VOCs per lifetime and a higher VOC index (p= 0.039, 0.034, 0.047, 0.040 and 0.008 respectively). Levels <500ng/ml predominated in SS (89.4%) than Sβ groups (70%) (p= 0.023) and in patients with high frequency of VOCs (91.4%) (p=0.008). Serum MBL level correlated negatively with patients’ age, disease duration, hydroxyurea total treatment duration, blood transfusions per lifetime and steady-state HbS level (p= <0.001, <0.001, 0.011, 0.014, 0.031 respectively) but correlated positively with steady-state HbF level (p=0.002). MBL (-221) X/Y both alleles were more associated with (H) allele of MBL (-550) than with L allele (p=0.048), however, with no statistically significant genotype distribution between the studied variants. There was no statistically significant difference in genotype distribution or allele frequencies between MBL (-221) and MBL (-550) in SCD patients regarding serum MBL level, sickle cell type (SS and Sβ), VOCs frequencies or disease severity classes. Conclusion: Serum MBL level rather than studied MBL gene variants is more likely to contribute to the clinical outcomes of SCD; patients with lower MBL levels had a higher rate of VOC per year, per lifetime and a higher VOC index. Meanwhile, the variant genotypes and alleles of the studied MBL promotor gene variants were not associated with MBL deficiency, VOCs, infection events, and disease severity.Further studies to investigate other polymorphisms in MBL gene; MBL exon-1 (codons 52,54 and 57) are recommended. Keywords: MBL, Polymorphism, Sickle cell disease, Vaso-occlusive crises, Egypt References 1. Medeiros et al, Genetics and Molecular Biology2017;40 (3): 600-603 2. De Pascale et al, Mediators of inflammation 2013; 268503